Abstract. Obesity is markedly associated with abnormal bone density indicating the importance of adipocytes in bone metabolism. However, the specific function of adipocytes remains unclear, with marked discrepancies in observations of previous studies. In the present study, the effect of adipocytes on osteoblasts/osteoclasts was analyzed. A mouse model of obesity was established and an in vitro co-culture system was utilized containing adipocyte and MC3T3/RAW 264.7 cells in a Transwell plate. Compared with control mice, obese mice exhibited low body weight and bone mineral density of the tibia and fat cells were observed to accumulate in bone marrow. MC3T3/RAW 264.7 cells were co-cultured with adipocytes and the mRNA and protein expression of alkaline phosphatase and osteocalcin was found to be decreased in MC3T3-E1 cells and mRNA and protein expression of tartrate-resistant acid phosphatase and cathepsin K was significantly increased in RAW 264.7 cells. In addition, the effect of adipocytes on the osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL)/RANK system indicated that the RANKL/OPG ratio secreted by osteoblasts increased and RANK expression by osteoclasts increased, leading to increased osteoclastogenesis. These results indicate that bone metabolism is impaired in obese mice leading to decreased osteoblastogenesis and marked increases in osteoclastogenesis and low bone mass.
IntroductionObesity is becoming increasingly prevalent, leading to reduced life expectancy and increased health problems (1). High body mass index (BMI) is associated with various diseases, including cardiovascular, obstructive sleep apnea, diabetes mellitus type 2, specific types of cancer and osteoarthritis (2). Bone metabolism is also abnormal in obesity (3) and positive and negative factors have been identified to be associated with bone health status (4-6). A number of previous studies have revealed that obesity stimulates bone formation by inhibiting apoptosis. A recent study demonstrated that high BMI prevents normal bone fracture and osteoporotic fracture in various age groups and genders (7). By contrast, it has also been reported that osteoporosis occurs in obese individuals (8). These inconsistencies may be due to the use of different animal models in each study.Adipose tissue, a large endocrine organ, secretes a number of hormones that affect bone metabolism. Adipocytes in the bone marrow microenvironment differentiate from bone marrow mesenchymal cells and secrete cytokines which affect osteoblast and osteoclast levels in bone marrow. The effect of adipocytes on osteoblasts/osteoclasts remains controversial.The aim of the present study was to identify the function of adipocytes in the bone marrow microenvironment. To analyze the biological foundations of bone metastasis in obesity, a high-fat diet was selected to establish a mouse model of obesity (9). The results indicate that adipocytes accumulate in the bone marrow environment and affect bone turnover and osteoblast/osteoclast differentiation....